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Daily Dose (daily + dose)
Kinds of Daily Dose Selected AbstractsWhat happened to the prescribing of other COX-2 inhibitors, paracetamol and non-steroidal anti-inflammatory drugs when rofecoxib was withdrawn in Australia?,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 11 2007Nadia Barozzi Abstract Objectives To analyse how the prescribing of cyclooxygenase-2 (COX-2) inhibitors, non-selective non-steroidal anti-inflammatory drugs (ns-NSAIDs) and paracetamol (acetaminophen) changed when rofecoxib was withdrawn in 2004. Method COX-2 inhibitors, paracetamol and ns-NSAID's use was measured using dispensing data for concession beneficiaries subsidized by the Australian Pharmaceutical Benefit Scheme (PBS) for the period of 1997,2005. Data were downloaded from the Medicare Australia website and converted, according to the World Health Organization (WHO) Anatomical Therapeutic Chemical (ATC)/Defined Daily Dose (DDD) (2005), to DDD/1000 concession beneficiaries/day. Results In the period 2000,2004, the use of COX-2 inhibitors was progressively increased. Overall NSAID's use changed from approximately 80 to 105,DDD/1000 concession beneficiaries/day while a decrease of ns-NSAIDs from about 70 to 40,DDD/1000 concession beneficiaries/day was observed. Following rofecoxib withdrawal, the overall NSAIDs use declined. In 2005, celecoxib prescription declined (23%) while prescription of meloxicam increased by 62%. Use of paracetamol was steady over the period 1997,2004 (around 40,DDD/1000 concession beneficiaries/day). In April 2005, a slight increase in paracetamol use was observed. Conclusion Our analysis showed that COX-2 inhibitors prescribing markedly influenced the overall NSAIDs prescribing in Australia. When COX-2 inhibitors were introduced their uptake was rapid and extensive. Following rofecoxib withdrawal, the total overall dispensing of NSAIDs returned to a similar value as before COX-2 inhibitors' introduction. The decrease was due both to rofecoxib withdrawal and to a reduction in celecoxib prescribing. However, meloxicam use increased. Paracetamol prescribing was steady, between 1997 and 2005 and was not affected when the COX-2 inhibitors were introduced on to the market and after rofecoxib withdrawal, rather than increasing as might have been anticipated after rofecoxib withdrawal. Copyright © 2007 John Wiley & Sons, Ltd. [source] Changes in prescribed drug doses after market introductionPHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 6 2002Eibert R. Heerdink PhD Abstract Purpose The establishment of recommended dosing regimens has always been a difficult aspect of drug development. This paper examines the extent to which postmarketing prescribing deviates from initially recommended dosing regimens. We used the World Health Organization's (WHO) periodically updated compilation of the ,Defined Daily Dose' (DDD) to reflect prevailing patterns of prescribing in national markets. The aim of this study was to evaluate DDD changes over time (1982,2000) and to identify possible determinants of these changes. Methods Data on DDD changes were obtained from the WHO's Oslo Collaborating Centre. We performed a case,control analysis in which we compared drugs with (cases) and without (controls) postmarketing changes in DDD on possible determinants associated with DDD change. Results We found 115 instances of a change of DDD in the period 1982,2000 (45 (39.1%) increases and 70 (60.9%) decreases). Antibiotics showed the greatest number of changes in DDD: predominantly increases in the 1980s, while the 1990s were dominated by decreases in DDD of mostly cardiovascular drugs. Conclusion Changes in DDD reflect the outcome of a melange of forces, including misconceptions of dose requirements during pre-market development of drug and postmarketing changes in pharmacotherapeutic knowledge, clinical concepts, economic forces, and, in the case of anti-infective agents, changing patterns of resistance/sensitivity of target microorganisms to the anti-infective agent(s) in question. Copyright © 2002 John Wiley & Sons, Ltd. [source] Amisulpride , dose, plasma concentration, occupancy and response: implications for therapeutic drug monitoringACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2009A. Sparshatt Objective:, To evaluate the relationships between dose, plasma concentration, pharmacological activity and clinical outcome to evaluate the appropriateness of therapeutic drug monitoring (TDM) in patients receiving amisulpride. Method:, Literature search of Embase, Medline and PubMed databases. Results:, Amisulpride plasma concentration is closely correlated with dose (r2 = 0.96, P < 0.0001), dopamine occupancy, response and with extra-pyramidal symptoms (EPS). Dose is correlated with response, dopamine occupancy and EPS. Optimal clinical response was found at doses of 400,800 mg/day, corresponding to plasma levels of approximately 200,500 ng/ml. EPS appears to be more reliably predicted by a plasma level above 320 ng/ml than by a particular dose. Conclusion:, The effects and safety of amisulpride in the treatment of schizophrenia and schizoaffective disorder are predicted by daily dose. The plasma concentration threshold for response appears to be approximately 200 ng/ml. EPS are more reliably predicted by plasma level than by dose. TDM for patients prescribed amisulpride is thus of some clinical value. [source] Pharmacokinetics of dipeptidylpeptidase-4 inhibitorsDIABETES OBESITY & METABOLISM, Issue 8 2010A. J. Scheen Type 2 diabetes (T2DM) is a complex disease combining defects in insulin secretion and insulin action. New compounds have been developed for improving glucose-induced insulin secretion and glucose control, without inducing hypoglycaemia or weight gain. Dipeptidylpeptidase-4 (DPP-4) inhibitors are new oral glucose-lowering agents, so-called incretin enhancers, which may be used as monotherapy or in combination with other antidiabetic compounds. Sitagliptin, vildaglipin and saxagliptin are already on the market in many countries, either as single agents or in fixed-dose combined formulations with metformin. Other DPP-4 inhibitors, such as alogliptin and linagliptin, are currently in late phase of development. The present paper summarizes and compares the main pharmacokinetics (PK) properties, that is, absorption, distribution, metabolism and elimination, of these five DPP-4 inhibitors. Available data were obtained in clinical trials performed in healthy young male subjects, patients with T2DM, and patients with either renal insufficiency or hepatic impairment. PK characteristics were generally similar in young healthy subjects and in middle-aged overweight patients with diabetes. All together gliptins have a good oral bioavailability which is not significantly influenced by food intake. PK/pharmacodynamics characteristics, that is, sufficiently prolonged half-life and sustained DPP-4 enzyme inactivation, generally allow one single oral administration per day for the management of T2DM; the only exception is vildagliptin for which a twice-daily administration is recommended because of a shorter half-life. DPP-4 inhibitors are in general not substrates for cytochrome P450 (except saxagliptin that is metabolized via CYP 3A4/A5) and do not act as inducers or inhibitors of this system. Several metabolites have been documented but most of them are inactive; however, the main metabolite of saxagliptin also exerts a significant DPP-4 inhibition and is half as potent as the parent compound. Renal excretion is the most important elimination pathway, except for linagliptin whose metabolism in the liver appears to be predominant. PK properties of gliptins, combined with their good safety profile, explain why no dose adjustment is necessary in elderly patients or in patients with mild to moderate hepatic impairment. As far as patients with renal impairment are concerned, significant increases in drug exposure for sitagliptin and saxagliptin have been reported so that appropriate reductions in daily dosages are recommended according to estimated glomerular filtration rate. The PK characteristics of DPP-4 inhibitors suggest that these compounds are not exposed to a high risk of drug,drug interactions. However, the daily dose of saxagliptin should be reduced when coadministered with potent CYP 3A4 inhibitors. In conclusion, besides their pharmacodynamic properties leading to effective glucose-lowering effect without inducing hypoglycaemia or weight gain, DPP-4 inhibitors show favourable PK properties, which contribute to a good efficacy/safety ratio for the management of T2DM in clinical practice. [source] Effects and serum levels of glibenclamide and its active metabolites in patients with type 2 diabetesDIABETES OBESITY & METABOLISM, Issue 6 2001A. Jönsson SUMMARY Objective To study the effects and serum levels of glibenclamide (Gb) and its active metabolites in patients on chronic Gb medication on different daily doses. Material and methods Fifty patients with type 2 diabetes on regular Gb therapy (1.75,14.0 mg daily). Blood samples were taken immediately before and 90 min after regular Gb intake. A standardized breakfast was served 30 min after drug intake. Serum insulin and proinsulin levels were determined by ELISA methods without cross-reactivities. Serum drug levels were determined by HPLC. Fischer's R to Z -test (correlation coefficients) and paired Student t -tests were used when comparing values within the entire group and unpaired non-parametric Mann,Whitney tests were used when comparing high and low dose levels. A p-value <,0.05 was considered significant. Results There were significant correlations between daily Gb dose, on the one hand, and, on the other, HbAlc (r = 0.55), ,-insulin (r = , 0.59) and ,-proinsulin (r = , 0.52) levels. Significant correlations between Gb therapy duration and insulin (r = , 0.40) and proinsulin (r = , 0.34) secretion and between Gb dose and ratio proinsulin/insulin (RPI) at both time points (r = 0.32 and 0.30) were also found. The RPI was lower after Gb intake. In patients on , 10.5 mg steady state serum metabolite levels (Ml and Ml + M2) were higher (29(0,120) and 33 (0,120) ng/ml) than those of Gb itself (18(0,64) ng/ml). A great inter-subject variability in Gb levels at both time points was seen. Conclusions Our results indicate that, in patients on chronic medication, Gb is capable of stimulating both insulin and proinsulin secretion; the effect on insulin release is relatively greater. The effect was more pronounced in patients on a low Gb dose, either because of less impaired ,-cells in those receiving low doses, or due to reduced sulphonylurea sensitivity in those on high dosage (down-regulation). In patients on a daily dose of 10.5 mg or more, serum metabolite levels of clinical relevance were demonstrated; the metabolites may contribute to hypoglycaemic events. [source] Interpretation of urinary concentrations of pseudoephedrine and its metabolite cathine in relation to doping controlDRUG TESTING AND ANALYSIS, Issue 5 2009K. Deventer Abstract Until the end of 2003 a urinary concentration of pseudoephedrine exceeding 25 µg/mL was regarded as a doping violation by the World Anti-Doping Agency. Since its removal from the prohibited list in 2004 the number of urine samples in which pseudoephedrine was detected in our laboratory increased substantially. Analysis of 116 in-competition samples containing pseudoephedrine in 2007 and 2008, revealed that 66% of these samples had a concentration of pseudoephedrine above 25 µg/mL. This corresponded to 1.4% of all tested in competition samples in that period. In the period 2001,2003 only 0.18% of all analysed in competition samples contained more than 25 µg/mL. Statistical comparison of the two periods showed that after the removal of pseudoephedrine from the list its use increased significantly. Of the individual sports compared between the two periods, only cycling is shown to yield a significant increase. Analysis of excretion urine samples after administration of a therapeutic daily dose (240 mg pseudoephedrine) in one administration showed that the threshold of 25 µg/mL can be exceeded. The same samples were also analysed for cathine, which has currently a threshold of 5 µg/mL on the prohibited list. The maximum urinary concentration of cathine also exceeded the threshold for some volunteers. Comparison of the measured cathine and pseudoephedrine concentrations only indicated a poor correlation between them. Hence, cathine is not a good indicator to control pseudopehedrine intake. To control the (ab)use of ephedrines in sports it is recommended that WADA reintroduce a threshold for pseudoephedrine. Copyright © 2009 John Wiley & Sons, Ltd. [source] Does prescribing for opiate addiction change after national guidelines?ADDICTION, Issue 5 2007Methadone, buprenorphine prescribing to opiate addicts by general practitioners, hospital doctors in England ABSTRACT Aim To assess changes in opiate prescribing (1995,2005) following a decade of national guidelines to address substandard opiate substitution prescribing for heroin addiction. Design A repeat national survey (1995 and 2005) using random one-in-four samples of all community pharmacies in England, achieving response rates of 75% (1847/2475) in 1995 and 95% (2349/2473) in 2005. Data were obtained on 3732 (1995 data) and 9620 (2005 data) prescriptions dispensed in the preceding month from the 936 and 1463 pharmacies who were currently dispensing. Measurements We have measured impact on practice for seven specific recommended changes. Findings Between 1995 and 2005 the number of substitute opiate prescriptions doubled (×2.03). By 2005, methadone still dominated (down from 97% to 83%), buprenorphine increased (from 1% to 16%) and other opiate medications virtually disappeared. Changes in the direction of national guidelines included: increased daily dose of methadone (from 47.3 mg to 56.3 mg), more frequent dispensing (from 38% to 60% as daily instalments), more supervised consumption (from 0% to 36%) and fewer methadone tablets (from 10.9% to 1.8%). Nevertheless, despite the increased mean daily dose, only 41.0% of prescriptions for methadone were for daily doses in the recommended 60,120 mg dose range. Only one change was not in the direction of the national guidelines,the proportion of prescriptions from GPs fell from 41% to 30%, although this still represented an approximate 50% increase in the extent of GP prescribing. Conclusion Doubling in provision of opiate substitute treatment has occurred, alongside significant improvements in the nature of this treatment. These positive changes have occurred in the direction of six out of seven of the UK national guidelines. [source] Relationship between adverse effects of antiepileptic drugs, number of coprescribed drugs, and drug load in a large cohort of consecutive patients with drug-refractory epilepsyEPILEPSIA, Issue 5 2010Maria Paola Canevini Summary Purpose:, To evaluate the adverse effects (AEs) of antiepileptic drugs (AEDs) in adults with refractory epilepsy and their relationship with number of coprescribed AEDs and AED load. Methods:, Patients with refractory epilepsy were enrolled consecutively at 11 tertiary referral centers. AEs were assessed through unstructured interview and the Adverse Event Profile (AEP) questionnaire. AED loads were calculated as the sum of prescribed daily dose (PDD)/defined daily dose (DDD) ratios for each coprescribed AED. Results:, Of 809 patients enrolled, 709 had localization-related epilepsy and 627 were on polytherapy. AED loads increased with increasing number of AEDs in the treatment regimen, from 1.2 ± 0.5 for patients on monotherapy to 2.5 ± 1, 3.7 ± 1.1, and 4.7 ± 1.1 for those on two, three, and ,4 AEDs, respectively. The number of spontaneously reported AEs correlated with the number of AEs identified by the AEP (r = 0.27, p < 0.0001). AEP scores did not differ between patients with monotherapy and patients with polytherapy (42.8 ± 11.7 vs. 42.6 ± 11.2), and there was no correlation between AEP scores and AED load (r = ,0.05, p = 0.16). Conclusions:, AEs did not differ between monotherapy and polytherapy patients, and did not correlate with AED load, possibly as a result of physicians' intervention in individualizing treatment regimens. Taking into account the limitations of a cross-sectional survey, these findings are consistent with the hypothesis that AEs are determined more by individual susceptibility, type of AEDs used, and physicians' skills, than number of coprescribed AEDs and AED load. [source] Developmental and Therapeutic Pharmacology of Antiepileptic DrugsEPILEPSIA, Issue 2000Hisao Miura Summary: We investigated the clinical effects and plasma levels of zonisamide (ZNS) in children with cryptogenic localization-related epilepsies. ZNS is absorbed slowly from the gastrointestinal tract, and its biological half-life is long as compared with that of other common antiepileptic drugs. The peak-to-trough plasma level ratios during a day were as small as 1.28 ± 0.15 in children taking a daily dose of 8 mg/kg of ZNS once a day as a single drug. The plasma level (,g/ml) to dose (mg/kg/day) ratios estimated by the trough and peak plasma levels both increased with advancing age, but the peak-to-trough plasma level ratios were maintained almost uniformly throughout the pediatric age period. A wide range of the plasma levels was associated with complete freedom from seizures. The range of the plasma levels in patients who did not respond to ZNS was higher than that in the controlled group. However, the clinical effects of ZNS were in agreement with the range of generally accepted therapeutic plasma levels of ZNS, 15,40 ,g/ml. Any patient who receives polytherapy is at risk to develop 1 or more drug interactions. Concurrent administration of carbamazepine (CBZ) decreases plasma concentrations of ZNS. However, ZNS does not alter plasma concentrations of CBZ or its primary metabolite, carbamazepine-10,11-epoxide (CBZ-E). It is evident that the concurrent administration of lamotrigine (LTG) affects plasma concentrations of CBZ-E, while plasma CBZ levels remain unaltered. However, the effect of LTG on plasma concentrations of CBZ-E is small, and none of the study patients showed toxic plasma concentrations of CBZ-E or associated clinical toxicity. Drug-protein binding interactions are another source of side effects. A simultaneous administration of valproic acid increases the total plasma CBZ-E levels relative to the CBZ dose associated with the raised free fractions of CBZ and CBZ-E. The high free plasma concentrations of CBZ-E above 1.5 ,g/ml may be responsible for the side effects. [source] Appraisal of current vitamin K dosing algorithms for the reversal of over-anticoagulation with warfarin: the need for a more tailored dosing regimenEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2006Elizabeth A. Sconce Abstract:, Warfarin is the most commonly prescribed oral anticoagulant in the UK for the treatment and prevention of thromboembolic disorders. Vitamin K administration is an effective way of reversing excessive anticoagulation. Over-anticoagulated patients present with a wide range of international normalized ratio (INR) values and may respond differently to a fixed dose of vitamin K. Current dosing algorithms for vitamin K administration in the non-urgent treatment of over-anticoagulation do not take this variability in response into account. Consequently, over a third of over-anticoagulated patients still remain outside their target INR 24 h after treatment. Such patients are therefore prone to either haemorrhage (if the patient is still over-anticoagulated) or thromboembolism (if the INR reversal is over-corrected). A number of factors such as patient age, body weight, co-morbidity, frailty, warfarin daily dose and CYP2C9 and VKORC1 polymorphism could affect response to vitamin K and thus the rate and extent of INR reversal. There is a need for a more individualized approach to the reversal of over-anticoagulation in asymptomatic or mildly haemorrhagic patients in order to improve the safety of warfarin therapy. [source] Dialysate concentration and pharmacokinetics of 2F-Ara-A in a patient with acute renal failureEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2005Jan T. Kielstein Abstract:, Fludarabine is frequently used for treatment of B-cell chronic lymphocytic leukemia and in conditioning regimes for hematopoietic cell transplantations. The total body clearance of the principal metabolite 2-fluoro-ara-A (2F-Ara-A) correlates with the creatinine clearance. We report data on total dialysate concentration as well as pharmacokinetics of 2F-Ara-A in a patient with anuric acute renal failure. On three consecutive days the patient received a daily dose of 80 mg (40 mg/m2) fludarabine and underwent three consecutive extended (daily) dialysis (ED) sessions. ED removed a considerable amount of the drug. The average dialysis clearance was 33.85 ml/min which is about 25% of the clearance in patients without renal failure. No toxic side effects of the treatment were observed. This case suggests that fludarabine treatment can be considered in patients requiring dialysis if dose reduction and adequate removal of the drug by hemodialysis is provided. [source] Subcutaneous histamine versus sodium valproate in migraine prophylaxis: a randomized, controlled, double-blind studyEUROPEAN JOURNAL OF NEUROLOGY, Issue 10 2007R. O. Millán-Guerrero Histamine has a selective affinity for H3-receptors and it may specifically inhibit the neurogenic edema response involved in migraine pathophysiology. The objective of this study was to evaluate the therapeutic potential of subcutaneous administration of histamine in migraine prophylaxis, compared with oral administration of sodium valproate, in an open clinical trial. Ninety-two patients with migraine were selected under criteria established by the International Headache Society and enrolled in a 12-week double-blind controlled clinical trial to evaluate the efficacy of subcutaneous administration of histamine (1,10 ng twice a week; n = 46) compared with oral administration of sodium valproate (500 mg daily dose; n = 46). The variables studied were headache intensity, frequency, duration, analgesic intake and migraine disability assessment (MIDAS). Two-tailed Student's t - test was used to compare means and the Mann,Whitney U and anova tests were used. The data collected during the 4th, 8th and 12th weeks of treatment revealed that histamine caused a significantly greater reduction (P < 0.001) in intensity and duration of migraine attacks as well as in analgesic intake. No difference was detected in the frequency of attacks or in MIDAS. The present study provides evidence of the superior efficacy of histamine applied subcutaneously in migraine prophylaxis when compared with sodium valproate taken orally. Subcutaneously applied histamine may represent a novel and effective therapeutic alternative in resistant migraine patients. [source] Ginkgo biloba and donepezil: a comparison in the treatment of Alzheimer's dementia in a randomized placebo-controlled double-blind studyEUROPEAN JOURNAL OF NEUROLOGY, Issue 9 2006M. Mazza The Ginkgo biloba special extract EGb 761 seems to produce neuroprotective effects in neurodegenerative diseases of multifactorial origin. There is still debate about the efficacy of Ginkgo biloba special extract EGb 761 compared with second-generation cholinesterase inhibitors in the treatment of mild to moderate Alzheimer's dementia. Our aim is to assess the efficacy of the Ginkgo biloba special extract E.S. in patients with dementia of the Alzheimer type in slowing down the disease's degenerative progression and the patients' cognitive impairment compared with donepezil and placebo. The trial was designed as a 24-week randomized, placebo-controlled, double-blind study. Patients aged 50,80 years, suffering from mild to moderate dementia, were allocated into one of the three treatments: Ginkgo biloba (160 mg daily dose), donepezil (5 mg daily dose), or placebo group. The degree of severity of dementia was assessed by the Syndrom Kurz test and the Mini-Mental State Examination. Clinical Global Impression score was recorded to assess the change in the patients' conditions and the therapeutic efficacy of tested medications. Our results confirm the clinical efficacy of Ginkgo biloba E.S. (Flavogin) in the dementia of the Alzheimer type, comparable with donepezil clinical efficacy. There are few published trials that have directly compared a cholinesterase inhibitor with Ginkgo for dementia. This study directly compares a cholinesterase inhibitor with Ginkgo biloba for dementia of the Alzheimer type and could be a valid contribution in this debate. Our study suggests that there is no evidence of relevant differences in the efficacy of EGb 761 and donepezil in the treatment of mild to moderate Alzheimer's dementia, so the use of both substances can be justified. In addition, this study contributes to establish the efficacy and tolerability of the Ginkgo biloba special extract E.S. in the dementia of the Alzheimer type with special respect to moderately severe stages. [source] Pergolide mesylate can improve sexual dysfunction in patients with Parkinson's disease: the results of an open, prospective, 6-month follow-upEUROPEAN JOURNAL OF NEUROLOGY, Issue 7 2004M. Pohanka One of the most disabling problems in males suffering from advanced Parkinson's disease (PD) is complex sexual dysfunction. The effect of dopamine replacement or dopaminergic stimulation on sexual dysfunction has been recently examined and described in patients treated by L-DOPA or apomorphine. Pergolide mesylate is another dopamine agonist with a known high affinity to hD(2S) subtype and a lower affinity to hD(2L) subtype of D2 dopaminergic receptors. It has been repeatedly shown to be a highly effective treatment of the complicated and advanced stages of PD. The current study has been designed to assess its efficacy in the treatment of sexual dysfunction, which frequently accompanies the complicated stage of PD in males. Fourteen male patients suffering from PD, each of whom had been treated with L-DOPA, and in whom additional treatment with peroral dopaminergic agonist (DA) was needed, were followed for a 6-month period. Pergolide mesylate (Permax) was given to each patient, and titrated to a total daily dose of 3 mg. All of the patients were taking L-DOPA. The assessments performed before the start of pergolide treatment consisted of a neurological examination, including Unified Parkinson's Disease Rating Scale (UPDRS) III and IV subscales scoring, Mini Mental State Examination (MMSE) scoring, the neuropsychological examination including Zung scale scoring to exclude depression, biochemical and haematological examinations including the examination of prolactine serum levels; and a sexological examination during which the patients filled-in the International Index of Erectile Function (IIEF) questionnaire. These examinations were repeated during the control assessments at months 1, 3 and 6. To compare the examination results, anova, Friedmann's anova (non-parametric) and Tukey post hoc tests were used. There were statistically significant differences between the values of UPDRS III motor subscale, UPDRS IV (complications of therapy) subscale and all subscales of IIEF when months 0 and 1 were compared with the results obtained at months 3 and 6. The differences between months 0 and 1 and months 3 and 6 (in these items) were virtually insignificant. In conclusion, pergolide substantially improved sexual function in the younger male patients who were still interested in sexual activities. In such cases, the introduction of pergolide might be a better choice than treatment with sildenafile, which usually meets several contraindications in common PD male population. [source] Pramipexole and pergolide in the treatment of depression in Parkinson's disease: a national multicentre prospective randomized studyEUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2003I. Rektorová An 8-month multicentre prospective randomized study aimed at comparing the effects of dopamine receptor agonists pramipexole (PPX; Mirapexin®) and pergolide (PRG; Permax®) as add-on to L-dopa therapy on depression [Montgomery and Asberg Depression Rating Scale (MADRS)] in 41 non-demented patients (25 men, 16 women) suffering from both mild or moderate depression and advanced Parkinson's disease (PD). The assessment was performed by a blinded independent observer. Motor symptoms (UPDRS III), motor complications (UPDRS IV), activities of daily living (UPDRS II and VI) and depressive symptoms as measured by Self , Rating Depression Scale by Zung were evaluated in an open-label design. The average value of Zung scores decreased significantly in both groups with no statistical difference between both groups. A significant decrease in the average value of MADRS scores was present only in the PPX group. The average UPDRS scores decreased significantly with no statistical difference between both groups at the comparable average total daily dose of both preparations. In both cases, the total daily dose of L-dopa decreased significantly but the decrease was statistically more pronounced in the PRG group. Our results demonstrate the antidepressant effect of PPX in patients with PD while we can't make any conclusions with regard to antidepressant effect of PRG. [source] Dextropropoxyphene withdrawal from a French university hospital: impact on analgesic drug consumptionFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2009Sabine Gaubert Abstract Dextropropoxyphene is a weak opioid analgesic, widely used as a step 2 analgesic (according to WHO classification) in combination with peripheral analgesics, mainly paracetamol. Recent data have underlined its poor analgesic efficacy (in comparison with paracetamol), risks of serious adverse drug reactions (i.e. hepatic reactions, hallucinations, abuse, withdrawal symptoms, hypoglycaemia), possible lethality after overdose, its risk of accumulation in patients with renal failure or in elderly people and some pharmacokinetic insufficiencies (i.e. different half-lives for dextropropoxyphene and paracetamol). Taking into account these data, the drug committee of the Toulouse University Hospital (France) decided to withdraw dextropropoxyphene from the hospital formulary since 1 June 2005. The aim of our study was to investigate the consequences of this withdrawal by comparing use of analgesic drugs in Toulouse University Hospital before (2004) and after (2006) dextropropoxyphene withdrawal (using defined daily dose for 1000 hospitalization-days as the unit measure). Before withdrawal, dextropropoxyphene (in combination with paracetamol) was the second most used analgesic drug after paracetamol alone. After dextropropoxyphene withdrawal, total consumption of analgesic drugs decreased by 4.6% (2006 vs. 2004). There was a 28% decrease in consumption of step 2 analgesics [with an increase in oral tramadol and a slight decrease in codeine (in combination with paracetamol)]. During the same period, step 1 analgesic consumption increased by 11% (mainly paracetamol) and that of step 3 analgesics slightly decreased (,8%). These results show that dextropropoxyphene withdrawal was not associated with a marked switch in prescriptions towards other analgesic drugs. This paper underlines the interest of a hospital-based drug committee to promote rational drug use. Finally, the present data allow us to discuss putative misuse of dextropropoxyphene. [source] Plasma antioxidative activity during atorvastatin and fluvastatin therapy used in coronary heart disease primary preventionFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2004Jan Kowalski Abstract We estimated the effect of atorvastatin and fluvastatin on plasma antioxidative activity used in coronary heart disease (CHD) primary prevention. Anti-oxidative activity of blood plasma was determined by Bartosz et al. method [Curr. Top. Biophys. (1998)22:11,13], based on reduction of preformed cation radical of 2,2,azinobis(3-ethylbenzothiazoline-6-sulphonic acid) by blood plasma. The study comprised 35 patients with CHD risk who were randomly divided into two groups. The atorvastatin group comprised 17 patients who were administered the drug orally in a daily dose of 10 mg and the fluvastatin group consisted of 18 patients on an oral dose of 40 mg once daily. The control group comprised 12 healthy subjects with no drug administration. Blood samples were collected from cubital vein before and after 6-week therapy. Significantly (P < 0.05) increased , in comparison with the initial values , antioxidative activity of blood plasma was found in atorvastatin and fluvastatin groups after 6-week therapy. Moreover, the increase in antioxidative plasma activity in atorvastatin group was significantly higher in comparison with the fluvastatin group. The results of our study have demonstrated that atorvastatin and fluvastatin have an additional mechanism independent of the effect on cholesterol concentration. Thus, we presume that administration of these statins in CHD risk patients may have a beneficial effect. [source] Antiepileptic Drugs in Migraine PreventionHEADACHE, Issue 2001Ninan T. Mathew MD Migraineurs may continue to experience attacks, despite daily use of one or more agents from a wide range of drugs, including , -blockers, calcium channel blockers, serotonin antagonists, tricyclic antidepressants, monoamine oxidase inhibitors, and antiepileptic agents. Divalproex sodium is the only antiepileptic drug approved for migraine prevention. Gabapentin, topiramate, and other antiepileptic agents are being evaluated for migraine prevention and treatment. Prospective, double-blind, placebo-controlled clinical trials of divalproex, gabapentin, and topiramate for migraine prevention generally were composed of a prospective baseline period, a dose titration period, and a fixed-dose treatment period. The primary efficacy variable was a reduction in the 28-day frequency of migraine headache. Patients receiving divalproex for 12 weeks at doses up to 1500 mg/day achieved significant decreases in the migraine frequency (P<.05), corresponding to reductions of 30% to 40% compared with baseline. Nearly half of the divalproex-treated patients had a 50% or more reduction from baseline in headache frequencies (P.05). Asthenia, vomiting, somnolence, tremor, and alopecia were common adverse events associated with divalproex. Significant reductions in migraine frequency were also observed with gabapentin (1800 to 2400 mg/day) when compared with placebo (P<.01), and nearly half of all patients treated at the highest dose experienced a reduction in headache rate of 50% or more. Somnolence was the most commonly reported adverse event among the gabapentin-treated patients. Two single-center, double-blind, placebo-controlled clinical trials evaluated topiramate for migraine prevention. A lower 28-day migraine frequency was seen during 18 weeks of administration at a maximum daily dose of 200 mg (P = .09). In a second study, a significantly lower mean 28-day migraine frequency was observed during 16 weeks of treatment with topiramate (P = .0015). Mean reduction in migraine frequency was also significantly greater in topiramate-treated patients (P = .0037). Paresthesias, diarrhea, somnolence, and altered taste were commonly reported adverse events in the topiramate-treated patients. Unlike some patients given divalproex or gabapentin, some given topiramate reported weight loss. Large, double-blind, placebo-controlled trials may prove the effectiveness of novel antiepileptic drugs in migraine prevention. [source] Guidelines for the treatment of chronic hepatitis and cirrhosis due to hepatitis C virus infection for the fiscal year 2008 in JapanHEPATOLOGY RESEARCH, Issue 1 2010Hiromitsu Kumada In the 2008 guidelines for the treatment of patients with chronic hepatitis C, pegylated interferon (Peg-IFN) combined with ribavirin for 48 weeks are indicated for treatment-naive patients infected with hepatitis C virus (HCV) of genotype 1. Treatment is continued for an additional 24 weeks (72 weeks total) in the patients who have remained positive for HCV RNA detectable by the real-time polymerase chain reaction at 12 weeks after the start of treatment, but who turn negative for HCV RNA during 13,36 weeks on treatment. Re-treatment is aimed to either eradicate HCV or normalize transaminase levels for preventing the development of hepatocellular carcinoma (HCC). For patients with compensated cirrhosis, the clearance of HCV RNA is aimed toward improving histological damages and decreasing the development of HCC. The recommended therapeutic regimen is the initial daily dose of 6 million international units (MIU) IFN continued for 2,8 weeks that is extended to longer than 48 weeks, if possible. IFN dose is reduced to 3 MIU daily in patients who fail to clear HCV RNA by 12 weeks for preventing the development of HCC. Splenectomy or embolization of the splenic artery is recommended to patients with platelet counts of less than 50 × 103/mm3 prior to the commencement of IFN treatment. When the prevention of HCC is at issue, not only IFN, but also liver supportive therapy such as stronger neo-minophagen C, ursodeoxycholic acid, phlebotomy, branched chain amino acids (BCAA), either alone or in combination, are given. In patients with decompensated cirrhosis, by contrast, reversal to compensation is attempted. [source] Possible predictors of response to clonazepam augmentation therapy in patients with protracted depressionHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 1 2007Shigeru Morishita Abstract Introduction Clonazepam has been shown to be an effective supplementary treatment for depression. Thus, it would be useful to determine which patient characteristics are associated with response to clonazepam. Aims The purpose of this study was to examine the possible predictors of response to clonazepam in the treatment of depression. Method A retrospective cohort analysis was carried out in 120 patients with protracted depression who were being treated with clonazepam. Results A variety of clinical factors, including age, gender, type of depression, frequency of episodes, family history; and daily dose of clonazepam, were analyzed as possible predictors of response to clonazepam. A Weibull regression analysis showed that the factors that best predicted improvement with clonazepam augmentation were negative family history of psychiatric illness (ecoef,=,0.378), daily clonazepam dose of 2.5,4.0,mg (ecoef,=,0.160), and unipolar depression (ecoef,=,0.147). Conclusions These factors should be considered when clonazepam augmentation therapy is selected for protracted depression. Copyright © 2007 John Wiley & Sons, Ltd. [source] How adherent to treatment with azathioprine are patients with Crohn's disease in long-term remission?INFLAMMATORY BOWEL DISEASES, Issue 4 2007Gerassimos J. Mantzaris MD Abstract Background: Patients with longstanding quiescent Crohn's disease on azathioprine usually maintain an excellent quality of life but are also concerned about long-term safety. This may affect adherence to treatment. The aim of the present study was to assess the adherence to azathioprine in a cohort of patients with Crohn's disease in long-term remission. Methods: Thirty patients with Crohn's disease in remission on azathioprine for ,48 months were enrolled in the study. All were asked to record the number of azathioprine tablets they consumed daily. Notes were kept every other month for 6 months. Adherence was defined as consumption of ,80% of medication. Results: Most patients (18/28, 74.3%) were not adherent to treatment. The mean (±SD) daily dose of azathioprine in adherent and nonadherent patients was 145 ± 45 mg and 102 ± 20 mg, respectively. However, there were no significant differences between the 2 groups in the mean IBDQ score and mean Crohn's Disease Activity Index (CDAI) score, both throughout the entire study and at each time point of the study. Male gender, single status, and consumption of >5 concomitant medications were associated with nonadherence. Conclusions: Most patients with Crohn's disease in longstanding remission had low self-reported adherence to azathioprine. Both male gender and single status were associated with nonadherence to azathioprine, whereas disease factors were not related to self-reported adherence. Patients considered nonadherent to treatment maintained disease remission and a quality of life similar to patients who were adherent to treatment. (Inflamm Bowel Dis 2006) [source] Lactate levels in Asian patients with type 2 diabetes mellitus on metformin and its association with dose of metformin and renal functionINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 11 2007Vivien C. C. Lim Summary Aim:, Our aims are to discover the average fasting plasma lactate level (FPL) in Asian patients with type 2 diabetes mellitus on metformin, with or without renal impairment and whether FPL is associated with the total daily dose of metformin (Tmet) and the degree of renal impairment in these patients. Methods:, We conducted an observational cross-sectional study of Asian patients with type 2 diabetes, using measurements of FPL levels and glomerular filtration rate (GFR) calculated, using the abbreviated modification of diet in renal disease (MDRD) formula. The association between FPL, Tmet, GFR and other potential predictors was analysed. Results:, A total of 97 subjects were recruited from our diabetes centre between July 2005 and February 2006. Sixty (61.9%) of the subjects were males; 69 (71.1%) Chinese, 21 (21.6%) Malays and 6 (6.2%) Indians. The mean (SD) age was 58.8 years (10.7) and the mean body mass index was 27.1 kg/m2 (5.3). The mean FPL was 1.8 mmol/l (0.9) with 20 (20.6%) of subjects having an FPL beyond the upper limit of our reference range of 2.2 mmol/l. The mean FPL (two SE) of subjects with Tmet of , 1000, 1001,2000 and > 2000 mg were 1.7 mmol/l (0.2), 1.6 mmol/l (0.2) and 2.1 mmol/l (0.5) respectively, (p = 0.119). The mean FPL of subjects with GFR of < 60, 60,90 and > 90 ml/min/1.73 m2 was 1.7 mmol/l (0.3), 1.8 mmol/l (0.3) and 1.8 mmol/l (0.4) respectively, p = 0.757. Among the potential predictors analysed, aspartate transaminase (p = 0.001) was found to be significantly associated with FPL. Conclusions:, Our study shows no correlation between Tmet and GFR with FPL in Asian type 2 diabetic patients on metformin. [source] The efficacy and safety of QVAR (hydrofluoroalkane-beclometasone diproprionate extrafine aerosol) in asthma (part 2): clinical experience in childrenINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 8 2004C. P. Van Schayck Summary QVAR [hydrofluoroalkane-134a beclometasone dipropionate (BDP)] produces equivalent asthma control to chlorofluorocarbon-based BDP inhalers, at approximately half the daily dose in adults, a probable consequence of the increased lung deposition of QVAR that results from its greater fine particle fraction. Recent studies have relied on the clinical experience with QVAR in adults as a basis for investigations in childhood asthma. Design considerations, such as the use of the breath-actuated AutohalerÔ delivery device and measurement of direct health benefits, account for problems of variation in inspiratory flow, handling difficulties and low airways resistance that are associated with children. QVAR appears to be well tolerated in children with no clinically relevant adverse effects on adrenal function, bone metabolism or growth at recommended doses. [source] Lichenoid nail changes as sole external manifestation of graft vs. host diseaseINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 1 2002Sara Isabel Palencia MD A 56-year-old-man who had refractory anemia with an excess of blasts underwent an allogeneic peripheral blood stem cell transplantation (PBSCT) from his brother after preparation with melphalan and fludarabin. He received GvHD (graft-vs.-host disease) prophylaxis with cyclosporine from day ,1 at a daily dose of 5 mg/kg of body weight. The daily dosage was tapered gradually from day +20. On post-PBSCT day 68 he developed acute cutaneous GvHD grade 3 and acute gastrointestinal GvHD grade 2,3, which was resolved with a daily dose of 1 mg/kg of body weight of prednisone. The patient was discharged in good clinical condition and without signs of GvHD, and he started tapering his immunosuppressive treatment. By day 160 he developed oral lichen planus-like changes, with several reticulate white lesions on the oral mucosa. A biopsy specimen was microscopically consistent with lichenoid GvHD (Fig. 1). By day 150 after PBSCT, when he was being treated with CsA 100 mg once daily and prednisone 10 mg once daily, his fingernails started to grow abnormally and gradually became dystrophic and painful. Two months later his toenails became similarly affected. Although affecting all finger and toe nails, the lesions were especially important in both thumbs. Physical examination revealed multiple findings on his nails (Fig. 2): thickening, fragility, onycholysis, longitudinal striations, and even pterygium. The micological cultures were negative. A biopsy specimen showed an sparse papillary dermis lymphoid infiltrate with focal exocytosis and presence of isolated multiple necrotic keratinocytes (Fig. 3). These findings were interpreted as a lichenoid GvHD with oral and nail involvement. The patient did not have other associated cutaneous lesions. He did not develop signs or symptoms consistent with hepatic GvHD. In May 2000 thalidomide was added to the immunosuppressive therapy, at a daily dose from 100 to 300 mg according to tolerance (constipation, sedation, ,). The lesions on the oral mucous showed a substantial improvement, but the nail changes remained more or less stable. Thalidomide was discontinued after 7 months because the patient displayed numbness and tingling in the hands and feet consistent with a peripheral neuropathy. Twenty days later he stopped taking thalidomide and the oral lichenoid lesions worsened, resulting in difficulty in eating. He also developed periungueal erythema, swelling and intense pain after minimal trauma. The daily dose of prednisone increased to 20,30 mg with moderate improvement. However, the dose could not be increased because of the secondary immunosuppressive effects. Twenty-three months post-PBSCT the patient remains with intense oral and nail lichenoid lesions. Figure Figure 1 . Oral mucosa with a lichenoid hiperplasia and a band-like lymphoid infiltrate. Note the basal lymphocytosis with isolated necrotic keratinocytes Figure 2. Lichenoid graft-vs.-host disease showing marked nail involvement with a ridge in the midline Figure 3. Panoramic view of the nail epithelium. Dermal lymphocytes with basal exocytosis and apoptotic keratinocytes (arrow) are evident [source] Hard palate perforation: an unusual finding in paracoccidioidomycosisINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 4 2001Luiz G. M. Castro MD A 36-year-old black man presented to his dermatologist in May 1996 complaining of mucosal lesions in the mouth, as well as perforation of the hard palate. The lesions had started approximately 7 months before and had worsened gradually. Other complaints included odynophagia, dysphagia, mild dyspnea, and dry cough. The patient was in good general health, but reported a 3 kg weight loss over the previous semester. The hard and soft palate presented erythematous ulcers with a finely granulated base and irregular, but clearly defined margins. A perforation (diameter, 0.5 cm) of the hard palate was seen in the center of the ulcerated region (Fig. 1). Direct examination of 10% KOH cleared specimens showed typical double-walled, multiple budding yeast structures. Paracoccidioidomycosis (PCM) serologic reactions tested positive for double immunodiffusion (DI), complement fixation (CF) 1 : 256 and counterimmunoelectrophoresis (CIE) 1 : 128. Hematoxylin and eosin-stained sections of oral lesions showed an ulcer covered by a fibrous leukocytic crust, with a lymphoplasmacytic infiltrate, as well as multinuclear giant cells containing round bodies with a double membrane. Gomori,Grocott staining showed budding and blastoconidia suggestive of PCM. Lung computed tomography (CT) exhibited findings consistent with pulmonary PCM. Diagnosis of the chronic multifocal form of PCM with oral and pulmonary manifestations was established. Drug therapy was initiated with ketoconazole (KCZ) 200 mg twice daily, which led to clinical cure in approximately 2 months. Serum antibody values rose 30 days after institution of therapy (CIE 1 : 256; CF 1 : 512), peaking at day 60 (CIE 1 : 1024; CF 1 : 1024). Three months later the daily dose was reduced to 200 mg and titers declined slowly. The diameter of the perforation remained unchanged (Fig. 2). The hard palate perforation was corrected with a palatoplasty 27 months after initiation of drug therapy (Fig. 3). KCZ was discontinued when serologic cure was achieved after 34 months of treatment (DI weakly positive; CIE 1 : 8; CF not measurable). The patient was discharged 46 months after the first visit. Figure 1. Ulcers with a finely granulated base on the hard palate with irregular but clearly defined margins. A perforation (diameter, 0.5 cm) of the hard palate is seen in the center of the ulcerated region Figure 2. Clinical aspect after 2 months of oral ketoconazole 200 mg twice daily. Resolution of ulceration was evident, but the diameter of the perforation remained unchanged Figure 3. Final result of palatoplasty to cover hard palate perforation [source] Severe antibody-mediated agranulocytosisINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 1 2008H. JOHNSEN Summary A 56-year-old female with Crohn's disease was admitted to the hospital with malaise, fever, and a low white blood cell count (0.8 × 109/l) with no granulocytes or myeloid precursor cells in the bone marrow. The leucopenia was initially thought to be the result of an infection and she was treated with antibiotics and granulocyte colony-stimulating factor (G-CSF, filgrastim). However, the bacterial cultures and viral tests were all negative. The patient's condition deteriorated and she became morbidly ill, but recovered after high dose steroid treatment. Six weeks later she relapsed whilst receiving 7.5 mg daily dose of prednisolone. She recovered quickly after being given high dose methylprednisolone in combination with filgrastim. A high maintenance dose of prednisolone was tapered over 5 months. She has not relapsed since and is currently well. Antibodies to the human neutrophil antigen (HNA)-3a were detected, but these antibodies could not easily explain her agranulocytosis as she had a HNA-3a negative phenotype. It seems plausible that her agranulocytosis was immune mediated through autoantibodies directed towards the early myeloid cells. [source] Oral estramustine phosphate and oral etoposide for the treatment of hormone-refractory prostate cancerINTERNATIONAL JOURNAL OF UROLOGY, Issue 7 2000Yoshiteru Sumiyoshi Abstract Background: The purpose of the present study was to evaluate the antitumor activity and toxicity of oral estramustine phosphate (EMP) in combination with oral etoposide in patients with hormone-refractory prostate cancer. Methods: Twenty patients with adenocarcinoma of the prostate that progressed after one or more regimens of androgen-deprivation therapy were enrolled into this trial. Oral EMP was administered twice daily, for a total daily dose of 560 mg, and oral etoposide (50 mg/bodyweight per day) was given on days 1,21 and was stopped on days 22,35. Treatment was continued until evidence of disease progression appeared or two consecutive rises in the prostate-specific antigen (PSA) value were observed. Results: Ten of 20 patients showed a decrease of 50% or greater in the PSA value from initially elevated PSA levels after therapy. The median progression-free duration and 2 year cause-specific survival rate of these 10 patients were 208 days (range 71,693 days) and 67.5%, respectively. There were no significant differences in age, pretreatment PSA value, duration from initial treatment to relapse, prior therapy or survival between patients who had a decrease of 50% or greater in PSA values after this combination therapy and those who did not. The main toxicities (, grade 2) were anemia, leukocytopenia, thrombocytopenia, gastrointestinal and hepatic disorders, which occurred in 40, 15, 10, 15 and 5% of patients, respectively. Conclusions: The combination of oral EMP and etoposide is considered to be a well-tolerated outpatient treatment regimen for patients with hormone-refractory prostate cancer and the therapy deserves further investigation. [source] Are All Commonly Prescribed Antipsychotics Associated with Greater Mortality in Elderly Male Veterans with Dementia?JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 6 2010Rebecca C. Rossom MD OBJECTIVES: To estimate mortality risk associated with individual commonly prescribed antipsychotics. DESIGN: Five-year retrospective study. SETTING: Veterans national healthcare data. PARTICIPANTS: Predominantly male, aged 65 and older, with a diagnosis of dementia and no other indication for an antipsychotic. Subjects who received an antipsychotic were compared with randomly selected controls who did not. Exposed and control cohorts were matched according to their date of dementia diagnosis and time elapsed from diagnosis to the start of antipsychotic therapy. MEASUREMENTS: Mortality during incident antipsychotic use. RESULTS: Cohorts who were exposed to haloperidol (n=2,217), olanzapine (n=3,384), quetiapine (n=4,277), or risperidone (n=8,249) had more comorbidities than their control cohorts. During the first 30 days, there was a significant increase in mortality in subgroups prescribed a daily dose of haloperidol greater than 1 mg (hazard ratio (HR)=3.2, 95% confidence interval (CI)=2.2,4.5, P<.001), olanzapine greater than 2.5 mg (HR=1.5, 95% CI=1.1,2.0, P=.01), or risperidone greater than 1 mg (HR=1.6, 95% CI=1.1,2.2, P=.01) adjusted for demographic characteristics, comorbidities, and medication history using Cox regression analyses. Greater mortality was not seen when a daily dose of quetiapine greater than 50 mg (HR=1.2, 95% CI=0.7,1.8, P=.50) was prescribed, and there was no greater mortality associated with a dose less than 50 mg (HR=0.7, 95% CI=0.5,1.0, P=.03). No antipsychotic was associated with greater mortality after the first 30 days. CONCLUSION: Commonly prescribed doses of haloperidol, olanzapine, and risperidone, but not quetiapine, were associated with a short-term increase in mortality. Further investigations are warranted to identify patient characteristics and antipsychotic dosage regimens that are not associated with a greater risk of mortality in elderly patients with dementia. [source] The Appropriateness of Drug Use in an Older Nondemented and Demented PopulationJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 3 2001Maria Stella T. Giron MD OBJECTIVE: To assess the extent of inappropriateness of drug use in an older nondemented and demented population. DESIGN: Descriptive analysis based on data from a sample of older subjects age 81 years and older. Data were collected from the second follow-up conducted in 1994,1996. SETTING: A population-based study of the Kungsholmen project in Stockholm, Sweden. PARTICIPANTS: Drug information was obtained from 681 subjects with a mean age of 86.9 years. The subjects were predominantly women (78%). Thirteen percent resided in institutions and 27.6% were diagnosed with dementia. MEASUREMENTS: Dementia diagnosis based on DSM III-R. Criteria for inappropriateness of drug use: use of drugs with potent anticholinergic properties, drug duplication, potential drug-drug and drug-disease interactions, and inappropriate drug dosage. RESULTS: The mean number of drugs used was 4.6: 4.5 drugs for nondemented and 4.8 for demented subjects. Nondemented subjects more commonly used cardiovascular-system drugs and demented subjects used nervous-system drugs. Demented subjects were more commonly exposed to drug duplication and to drugs with potent anticholinergic properties, both involving the use of psychotropic drugs. Nondemented subjects were more commonly exposed to potential drug-disease interactions, mostly with the use of cardiovascular drugs. The most common drug combination leading to a potential interaction was the use of digoxin with furosemide, occurring more frequently among nondemented subjects. The most common drug-disease interaction was the use of beta-blockers and calcium antagonists in subjects with congestive heart failure. The doses of drugs taken by both nondemented and demented subjects were mostly lower than the defined daily dose. CONCLUSION: There was substantial exposure to presumptive inappropriateness of drug use in this very old nondemented and demented population. The exposure of demented subjects to psychotropic drugs and nondemented subjects to cardiovascular drugs reflect the high frequency of prescribing these drugs in this population. [source] Endogenous antioxidant defence system in rat liver following mercury chloride oral intoxicationJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 3 2005Inmaculada Bando Abstract Mercury is a highly toxic metal which induces oxidative stress. Superoxide dismutases, catalase, and glutathion peroxidase are proteins involved in the endogenous antioxidant defence system. In the present study rats were administered orally, by gavage, a single daily dose of HgCl2 for three consecutive days. In order to find a relation between the proteins involved in the antioxidant defence and mercury intoxication, parameters of liver injury, redox state of the cells, as well as intracellular protein levels and enzyme activities of Mn-dependent superoxide dismutase (MnSOD), Cu-Zn-dependent superoxide dismutase (CuZnSOD), catalase, and glutathione peroxidase (GPx) were assayed both in blood and in liver homogenates. HgCl2 at the doses of 0.1 mg/kg produced liver damage which that was detected by a slight increase in serum alanine aminotransferase and gamma glutamyl transferase. Hepatic GSH/GSSG ratio was assayed as a parameter of oxidative stress and a significant decrease was detected, as well as significant increases in enzyme activities and protein levels of hepatic antioxidant defence systems. Changes in both MnSOD and CuZnSOD were parallel to those of liver injury and oxidative stress, while the changes detected in catalase and GPx activities were progressively increased along with the mercury intoxication. Other enzyme activities related to the glutathione redox cycle, such as glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PDH), also increased progressively. We conclude that against low doses of mercury that produce a slight oxidative stress and liver injury, the response of the liver was to induce the synthesis and activity of the enzymes involved in the endogenous antioxidant system. The activities of all the enzymes assayed showed a rapidly induced coordinated response. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 19:154,161, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20067 [source] | ||||||||||||||||||||||||||||||||||||||||